| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communications |
From the Departments of Pathology*
and
Oncology,
Johns Hopkins University School of
Medicine, Baltimore, Maryland
Decreased expression of the epithelial cell adhesion protein E-Cadherin occurs in several forms of human epithelial-derived cancers, including bladder cancers. We investigated the possibility that aberrant methylation of the CpG island flanking the 5' transcriptional start site of the e-cadherin gene is responsible for the decreased expression of this gene in bladder cancer, similar to the relationship previously seen between e-cadherin methylation and gene expression in other types of human cancers. Using methylation-specific polymerase chain reaction, we found methylation of this CpG island in 20 of 47 cases (43%) of bladder neoplasms ranging from low-grade papillary neoplasms to advanced, invasive cancers. When methylation status was compared to immunochemical staining for E-Cadherin, we found significantly diminished levels of E-Cadherin expression in 14 of 15 cases (93%) with methylation of the gene. We also found decreased expression of E-Cadherin, although to a somewhat lesser extent, in a high percentage (77%) of the cases without methylation of the gene. Although these data suggest a relationship between e-cadherin CpG island methylation and decreased gene expression, it evident that other mechanisms also contribute to decreased expression of this gene in bladder neoplasia. Remarkably, we also found low levels of e-cadherin methylation in urothelial cells from three of nine (33%) histologically normal bladders, with all three of the normal bladder samples with methylated e-cadherin being from individuals older than 70 years of age. Thus, methylation of the e-cadherin CpG island may occur normally in this tissue with aging as well as in low-grade papillary neoplasms, and is not specific to cancer in the bladder. This finding of methylation in normal urothelial cells from elderly individuals is provocative with respect to a possible link between aging and increased risk for bladder cancer, but it suggests limitations on the usefulness of using methylation of e-cadherin as a molecular marker for detection of bladder cancer.
This article has been cited by other articles:
 |
|
 |
|
  M. Kawaguchi, T. Toyama, R. Kaneko, T. Hirayama, Y. Kawamura, and T. Yagi Relationship between DNA Methylation States and Transcription of Individual Isoforms Encoded by the Protocadherin-{alpha} Gene Cluster J. Biol. Chem., May 2, 2008; 283(18): 12064 - 12075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Leung, E. P.S. Man, J. Yu, M. Y.Y. Go, K.-f. To, Y. Yamaoka, V. Y.Y. Cheng, E. K.W. Ng, and J. J.Y. Sung Effects of Helicobacter pylori Eradication on Methylation Status of E-Cadherin Gene in Noncancerous Stomach. Clin. Cancer Res., May 15, 2006; 12(10): 3216 - 3221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tominaga, S. Fujii, K. Mukawa, M. Fujita, K. Ichikawa, S. Tomita, Y. Imai, K. Kanke, Y. Ono, A. Terano, et al. Prediction of Colorectal Neoplasia by Quantitative Methylation Analysis of Estrogen Receptor Gene in Nonneoplastic Epithelium from Patients with Ulcerative Colitis Clin. Cancer Res., December 15, 2005; 11(24): 8880 - 8885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Friedrich, D. J. Weisenberger, J. C. Cheng, S. Chandrasoma, K. D. Siegmund, M. L. Gonzalgo, M. I. Toma, H. Huland, C. Yoo, Y. C. Tsai, et al. Detection of Methylated Apoptosis-Associated Genes in Urine Sediments of Bladder Cancer Patients Clin. Cancer Res., November 15, 2004; 10(22): 7457 - 7465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Maruya, J.-P. J. Issa, R. S. Weber, D. I. Rosenthal, J. C. Haviland, R. Lotan, and A. K. El-Naggar Differential Methylation Status of Tumor-Associated Genes in Head and Neck Squamous Carcinoma: Incidence and Potential Implications Clin. Cancer Res., June 1, 2004; 10(11): 3825 - 3830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dulaimi, R. G. Uzzo, R. E. Greenberg, T. Al-Saleem, and P. Cairns Detection of Bladder Cancer in Urine by a Tumor Suppressor Gene Hypermethylation Panel Clin. Cancer Res., March 15, 2004; 10(6): 1887 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Waki, G. Tamura, T. Tsuchiya, K. Sato, S. Nishizuka, and T. Motoyama Promoter Methylation Status of E-Cadherin, hMLH1, and p16 Genes in Nonneoplastic Gastric Epithelia Am. J. Pathol., August 1, 2002; 161(2): 399 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Maier and A. Olek Diabetes: A Candidate Disease for Efficient DNA Methylation Profiling J. Nutr., August 1, 2002; 132(8): 2440S - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tada, M. Wada, K.-i. Taguchi, Y. Mochida, N. Kinugawa, M. Tsuneyoshi, S. Naito, and M. Kuwano The Association of Death-associated Protein Kinase Hypermethylation with Early Recurrence in Superficial Bladder Cancers Cancer Res., July 15, 2002; 62(14): 4048 - 4053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Y. Chan, L. W. Chan, N. L. S. Tang, J. H. M. Tong, K. W. Lo, T. L. Lee, H. Y. Cheung, W. S. Wong, P. S. F. Chan, F. M. M. Lai, et al. Hypermethylation of Multiple Genes in Tumor Tissues and Voided Urine in Urinary Bladder Cancer Patients Clin. Cancer Res., February 1, 2002; 8(2): 464 - 470. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
